Impedance measuring device for biological samples and impedance measuring system for biological samples

ABSTRACT

Provided is an impedance measuring device for biological samples including one or a plurality of biological sample holding units configured to hold a biological sample, an applying unit configured to apply an AC voltage to a pair of electrodes in contact with the biological sample held by the biological sample holding unit, a measuring unit configured to measure an impedance of the biological sample obtained by an AC voltage being applied to the biological sample by the applying unit, and a measurement condition control unit configured to control a measuring time and/or a measuring frequency in the measuring unit.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a U.S. National Stage Application under 35 U.S.C. §371, based on International Application No. PCT/JP2013/084887, filedDec. 26, 2013, which claims priority to Japanese Patent Applications JP2013-013134, filed Jan. 28, 2013, each of which is hereby incorporatedby reference in its entirety.

TECHNICAL FIELD

The present technology relates to an impedance measuring device forbiological samples. More specifically, the present technology relates toan impedance measuring device for biological samples and an impedancemeasuring system for biological samples capable of automaticallyperforming the impedance measurement of a biological sample.

BACKGROUND ART

There are cases where the electrical characteristics of a biologicalsample are measured and the measurement results are used to determinethe properties of the sample or to discriminate the types of cells etc.contained in the sample (e.g. see Patent Literature 1). As theelectrical characteristics to be measured, complex dielectric constantand its frequency dispersion (dielectric spectrum) are given. Thecomplex dielectric constant and its frequency dispersion are generallycalculated by using a solution holder or the like including electrodesfor applying a voltage to a solution and measuring the complexcapacitance or the complex impedance between the electrodes.

Furthermore, for example, Patent Literature 2 discloses a technology inwhich information on blood coagulation is acquired from the dielectricconstant of blood, and describes “a blood coagulation system analyzingdevice including a pair of electrodes, applying means for applying an ACvoltage to the pair of electrodes at prescribed time intervals,measuring means for measuring the dielectric constant of blood disposedbetween the pair of electrodes, and analyzing means for analyzing thedegree of working of a blood coagulation system using the dielectricconstant of blood measured at the time intervals after the anticoagulanteffect working on the blood is removed.”

Furthermore, for example, Patent Literature 3 discloses a blood cellanalyzing device capable of evaluating effects and side effects of adrug in a short time by including a measuring unit that measures thecomplex dielectric constant spectrum of a suspension containing one or aplurality of blood cells, a detection unit that calculates thedielectric variable and/or the electrical property value of thesuspension on the basis of the complex dielectric constant spectrummeasured in the measuring unit and uses the calculated value to detect acondition change of the blood cell accompanying drug administration.

CITATION LIST Patent Literature

Patent Literature 1: JP 2009-042141A

Patent Literature 2: JP 2010-181400A

Patent Literature 3: JP 2011-112497A

SUMMARY OF INVENTION Technical Problem

As described above, there are cases where the impedance of a biologicalsample is measured to obtain various pieces of information on thebiological sample or to analyze the condition of the biological sample.To enhance measurement precision, it is very important to finely set themeasurement conditions etc. of the impedance in accordance with thetype, analysis objective, etc. of the biological sample.

However, in conventional devices, there have been cases where it isnecessary to set the measurement conditions each time in accordance withthe type, analysis objective, etc. of the biological sample and thecondition setting takes a long time in order to enhance measurementprecision.

Thus, a main object of the present technology is to provide, in theimpedance measurement of a biological sample, a measuring device capableof improving measurement precision rapidly in accordance with the type,analysis objective, etc. of the biological sample.

Solution to Problem

That is, according to the present technology, first, there is providedan impedance measuring device for biological samples including one or aplurality of biological sample holding units configured to hold abiological sample, an applying unit configured to apply an AC voltage toa pair of electrodes in contact with the biological sample held by thebiological sample holding unit, a measuring unit configured to measurean impedance of the biological sample obtained by an AC voltage beingapplied to the biological sample by the applying unit, and a measurementcondition control unit configured to control a measuring time and/or ameasuring frequency in the measuring unit.

In control of the measuring time in the measurement condition controlunit, a measuring interval in the measuring unit may be controlled.

In control of the measuring time in the measurement condition controlunit, a timing of measurement completion in the measuring unit may becontrolled.

The impedance measuring device for biological samples according to thepresent technology may include a temperature control unit configured tocontrol a temperature in the biological sample holding unit.

In the biological sample holding unit, a biological sample may be heldby holding a container in which the biological sample is stored.

The impedance measuring device for biological samples according to thepresent technology may include a biological sample supplying unitconfigured to supply the biological sample to the biological sampleholding unit automatically.

The impedance measuring device for biological samples according to thepresent technology may include a drug supplying unit configured tosupply one or more kinds of drug to the biological sample holding unitautomatically.

One or more kinds of drug may be stored in the container beforehand.

An example of the biological sample that can be measured by theimpedance measuring device according to the present technology is thebiological sample containing a blood component.

The impedance measuring device for biological samples according to thepresent technology may include a blood condition analyzing unitconfigured to analyze a condition change of blood from a temporal changeof an impedance measured in the measuring unit.

The impedance measuring device for biological samples according to thepresent technology may include a precision managing unit configured toperform management of precision of the measuring unit.

The impedance measuring device for biological samples according to thepresent technology may further include a driving mechanism configured tomove the biological sample holding unit.

In this case, the driving mechanism may move the biological sampleholding unit in a direction that changes a direction of gravity appliedto the biological sample held by the biological sample holding unit.

In addition, the impedance measuring device for biological samplesaccording to the present technology may include a stirring mechanismconfigured to perform stirring in the biological sample holding unit.

Next, according to the present technology, there is provided animpedance measuring system for biological samples including one or aplurality of biological sample holding units configured to hold abiological sample, an applying unit configured to apply an AC voltage toa pair of electrodes in contact with the biological sample held by thebiological sample holding unit, a measuring unit configured to measurean impedance of the biological sample obtained by an AC voltage beingapplied to the biological sample by the applying unit, a measurementcondition control unit configured to control a measuring time and/or ameasuring frequency in the measuring unit, a display unit configured todisplay data of an impedance measured in the measuring unit, and a userinterface for a user's operation.

The impedance measuring system for biological samples according to thepresent technology may include a memory unit configured to store data ofan impedance measured in the measuring unit.

Advantageous Effects of Invention

An impedance measuring device for biological samples according to thepresent technology can automatically control the measuring time and/orthe measuring frequency, and can therefore, in the impedance measurementof a biological sample, improve measurement precision rapidly inaccordance with the type, analysis objective, etc. of the biologicalsample.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a schematic conceptual diagram schematically showing theconcept of an impedance measuring device for biological samples 1according to the present technology.

FIG. 2 is a schematic cross-sectional view schematically showing anaspect of a biological sample holding unit 2 in the impedance measuringdevice for biological samples 1 according to the present technology.

FIG. 3 is a schematic cross-sectional view schematically showing anaspect of a connection unit 32 in the impedance measuring device forbiological samples 1 according to the present technology; FIG. A is aschematic cross-sectional view showing a state at the time ofnon-measurement, and FIG. B is a schematic cross-sectional view showinga state at the time of measurement.

FIG. 4 is a schematic cross-sectional view schematically showing anaspect of a driving mechanism 11 in the impedance measuring device forbiological samples 1 according to the present technology.

FIG. 5 is a conceptual diagram showing a stirring method when abiological sample S and a reagent R are stirred by pipetting using astirring mechanism 13.

FIG. 6 is a schematic conceptual diagram schematically showing theconcept of an impedance measuring system for biological samples 100according to the present technology.

FIG. 7 is a drawing-substitute graph showing an example of datadisplayed on a display unit in the impedance measuring system forbiological samples 100 according to the present technology.

DESCRIPTION OF EMBODIMENTS

Hereinbelow, preferred embodiments for carrying out the presenttechnology are described with reference to the drawings. The embodimentsdescribed below are examples of the typical embodiments of the presenttechnology, and the scope of the present technology is not construed asbeing limited by the embodiments. The description is given in thefollowing order:

1. Impedance measuring device for biological samples 1

(1) Biological sample holding unit 2

-   -   (a) Container 21    -   (b) Container holding unit 22

(2) Applying unit 3

-   -   (a) Electrodes 31 a and 31 b    -   (b) Connection unit 32

(3) Measuring unit 4

(4) Measurement condition control unit 5

(5) Temperature control unit 6

(6) Biological sample supplying unit 7

(7) Drug supplying unit 8

(8) Biological sample S

(9) Blood condition analyzing unit 9

(10) Precision managing unit 10

(11) Driving mechanism 11

(12) Sample standby unit 12

(13) Stirring mechanism 13

2. Impedance measuring system for biological samples 100

(1) Display unit 101

(2) User interface 102

(3) Memory unit 103

1. Impedance Measuring Device for Biological Samples 1

FIG. 1 is a schematic conceptual diagram schematically showing theconcept of an impedance measuring device for biological samples 1according to the present technology. The impedance measuring device forbiological samples 1 according to the present technology includes, interms of broad categories, at least a biological sample holding unit 2,an applying unit 3, a measuring unit 4, and a measurement conditioncontrol unit 5. The impedance measuring device for biological samples 1may include, as necessary, a temperature control unit 6, a biologicalsample supplying unit 7, a drug supplying unit 8, a blood conditionanalyzing unit 9, a precision managing unit 10, a driving mechanism 11,a sample standby unit 12, a stirring mechanism 13, etc. Each componentwill now be described in detail.

(1) Biological Sample Holding Unit 2

The biological sample holding unit 2 is a part where a biological sampleof the measuring object is held. In the impedance measuring device forbiological samples 1 according to the present technology, the number ofbiological sample holding units 2 is not particularly limited, and oneor a plurality of biological sample holding units 2 may be freelydisposed in accordance with the amount, type, measurement objective,etc. of the biological sample of the measuring object.

In the impedance measuring device for biological samples 1 according tothe present technology, impedance measurement is performed in a statewhere a biological sample S is held by the biological sample holdingunit 2. Hence, the biological sample holding unit 2 is preferably in aconfiguration capable of being sealed in the state of holding thebiological sample S. However, the biological sample holding unit 2 maynot be in an airtight configuration to the extent that it is capable ofbeing stationary through the time needed to measure the impedance of thebiological sample S and there is no influence on measurement.

Specific methods for introducing the biological sample S into thebiological sample holding unit 2 and for making sealing are notparticularly limited, and the introduction may be made by an arbitrarymethod in accordance with the configuration of the biological sampleholding unit 2. For example, although not shown in the drawings, amethod in which the biological sample holding unit 2 is provided with alid, and the biological sample S is introduced using a pipette or thelike and then the lid is closed to make sealing, a method in which thebiological sample holding unit 2 is pierced with a needle from its outersurface, and a biological sample S in a liquid form is injected and thenthe portion pierced with the needle is sealed with grease or the like tomake sealing, etc. are given.

The configuration of the biological sample holding unit 2 is notparticularly limited to the extent that the biological sample of themeasuring object can be held in the device, and may be designed to be anarbitrary configuration. For example, one or a plurality of cellsprovided on a substrate may be allowed to function as the biologicalsample holding unit 2, or one or a plurality of containers may beallowed to function as the biological sample holding unit 2. An aspectof the biological sample holding unit 2 will now be described withreference to FIG. 2.

FIG. 2 is a schematic cross-sectional view schematically showing anaspect of the biological sample holding unit 2 in the impedancemeasuring device for biological samples 1 according to the presenttechnology. The biological sample holding unit 2 illustrated in FIG. 2is formed of a container 21 and a container holding unit 22.

In the impedance measuring device for biological samples 1 according tothe present technology, when the container holding unit 22 is designedso that a known cartridge-type container for measurement can be used asthe container 21, the container holding unit 22 by itself can be made tofunction as the biological sample holding unit 2. That is, thebiological sample holding unit 2 in the impedance measuring device forbiological samples 1 according to the present technology includes all ofthe case of being formed of only the container 21, the case of beingformed of the container 21 and the container holding unit 22, and thecase of being formed of only the container holding unit 22.

(a) Container 21

In the impedance measuring device for biological samples 1 according tothe present technology, in the case where the container 21 is used asthe biological sample holding unit 2, specific configurations of thecontainer 21 are not particularly limited, and may be freely designed inaccordance with the condition, type, etc. of the biological sample S tothe extent that the biological sample S of the measuring object can beheld, including a circular cylindrical body, a polygonal cylindricalbody with a polygonal cross section (triangle, quadrangle, or polygonwith more angles), a conical body, a polygonal pyramid-like body with apolygonal cross section (triangle, quadrangle, or polygon with moreangles), or a configuration in which one or more of these are combined.

Also the material that forms the container 21 is not particularlylimited, and may be freely selected to the extent that there is noinfluence on the condition, type, measurement objective, etc. of thebiological sample S of the measuring object. In the present technology,in particular, the container 21 is preferably formed using a resin fromthe viewpoint of the ease of processing and molding etc. In the presenttechnology, also the type of usable resin is not particularly limited,and one or more types of resin usable for the holding of the biologicalsample S may be freely selected for use. For example, a hydrophobic andinsulating polymer such as polypropylene, poly(methyl methacrylate),polystyrene, an acrylic, a polysulfone, and polytetrafluoroethylene, acopolymer and a blend polymer thereof, and the like are given. In thepresent technology, the biological sample holding unit 2 is preferablyformed of, among the above materials, particularly one or more types ofresin selected from polypropylene, polystyrene, an acrylic, and apolysulfone. These resins have the property of being lowcoagulation-active against blood, and can therefore be suitably used forthe measurement of a biological sample containing blood, for example.

(b) Container Holding Unit 22

In the impedance measuring device for biological samples 1 according tothe present technology, in the case where the container holding unit 22is used as the biological sample holding unit 2, specific configurationsof the container holding unit 22 are not particularly limited, and thecontainer holding unit 22 may be freely designed to the extent that thecontainer 21 in which the biological sample S of the measuring object isstored can be held.

Also the material that forms the container holding unit 22 is notparticularly limited, and may be freely selected in accordance with theconfiguration etc. of the container 21 that the container holding unit22 holds.

(2) Applying Unit 3

The applying unit 3 is a part that applies an AC voltage to a pair ofelectrodes 31 a and 31 b that are in contact with the biological sampleS held by the biological sample holding unit 2. The applying unit 3applies a voltage to the pair of electrodes 31 a and 31 b from, as thestarting time point, the time point at which an order to startmeasurement is received or the time point at which the power supply forthe impedance measuring device for biological samples 1 is set to ON.More specifically, the applying unit 3 applies an AC voltage with a setfrequency or a frequency controlled in the measurement condition controlunit 5 described later to the electrodes 31 a and 31 b, at set measuringintervals or measuring intervals controlled in the measurement conditioncontrol unit 5 described later.

In the applying unit 3, it is also possible to apply an AC voltage to aplurality of pairs of electrodes. As the method for applying an ACvoltage to a plurality of pairs of electrodes, for example, a method inwhich the application of an AC voltage to a plurality of pairs ofelectrodes is performed simultaneously by a plurality of applying units3 being provided, a method in which the application of an AC voltage toa plurality of pairs of electrodes is performed by scanning one applyingunit 3, a method in which the application of an AC voltage to aplurality of pairs of electrodes is performed by moving the biologicalsample holding unit 2 including electrodes, a method in which aplurality of applying units 3 are provided and switching is performed toselect one or a plurality of applying units 3 that actually performapplication, etc. may be given.

(a) Electrodes 31 a and 31 b

The electrodes 31 a and 31 b are used to be in contact with thebiological sample S at the time of measurement and apply a necessaryvoltage to the biological sample S. In the impedance measuring devicefor biological samples 1 according to the present technology, thenumbers of electrode units 31 a and 31 b are not particularly limited tothe extent that the impedance of the biological sample S can bemeasured, and one or more pairs of electrodes may be freely arranged.

Also the arrangement, configuration, etc. of the electrodes 31 a and 31b are not particularly limited, and may be freely designed in accordancewith the configuration etc. of the biological sample holding unit 2 tothe extent that a necessary voltage can be applied to the biologicalsample S. For example, it is possible, like the biological sampleholding unit 2 shown in FIG. 2, to form the electrodes 31 a and 31 bintegrally with the biological sample holding unit 2 (the container 21),or it is possible, although not shown in the drawings, to employ aconfiguration in which the lid of the container 21 is provided with theelectrodes 31 a and 31 b and sealing is made by the lid to allow theelectrodes 31 a and 31 b to be in contact with the biological sample Sstored in the container 21. Furthermore, it is also possible to employ aconfiguration in which, at the time of measurement, a pair of electrodes31 a and 31 b are inserted into the container 21 from the outside of thecontainer 21 to allow the electrodes 31 a and 31 b to be in contact withthe biological sample S.

Also the material that forms the electrodes 31 a and 31 b is notparticularly limited, and one or more types of known electricallyconductive material may be freely selected for use to the extent thatthere is no influence on the condition, type, measurement objective,etc. of the biological sample S of the measuring object. For example,titanium, aluminum, stainless steel, platinum, gold, copper, graphite,and the like are given. In the present technology, the electrodes 31 aand 31 b are preferably formed of, among the above materials,particularly an electrically conductive material containing titanium.Titanium has the property of being low coagulation-active against blood,and can therefore be suitably used for the measurement of a biologicalsample containing blood, for example.

(b) Connection Unit 32

A connection unit 32 is a part that electrically connects the applyingunit 3 and/or the measuring unit 4 and the electrodes 31 a and 31 b.Specific configurations of the connection unit 32 are not particularlylimited, and the connection unit 32 may be designed in an arbitraryconfiguration to the extent that the applying unit 3 and/or themeasuring unit 4 and the electrodes 31 a and 31 b can be electricallyconnected. An aspect of the connection unit 32 will now be describedwith reference to FIG. 3.

FIG. 3 is a schematic cross-sectional view schematically showing anaspect of the connection unit 32 in the impedance measuring device forbiological samples 1 according to the present technology. FIG. 3A showsa state at the time of non-measurement, and FIG. 3B shows a state at thetime of measurement. The connection unit 32 illustrated in FIG. 3 isconfigured so that at the time of non-measurement, the applying unit 3and/or the measuring unit 4 and the electrodes 31 a and 31 b are in anon-connection state, and at the time of measurement, the applying unit3 and/or the measuring unit 4 and the electrodes 31 a and 31 b can beelectrically connected.

Specifically, the container 21 and the connection unit 32 on thecontainer 21 side, the connection unit 32 on the side of the applyingunit 3 and/or the measuring unit 4, or all of them are configured to bedrivable. At the time of non-measurement, the connection unit 32 on thecontainer 21 side and the connection unit 32 on the side of the applyingunit 3 and/or the measuring unit 4 are set to a non-contact state; andat the time of measurement, the connection unit 32 on the container 21side and the connection unit 32 on the side of the applying unit 3and/or the measuring unit 4 are driven into a contact state. Thus, theapplying unit 3 and/or the measuring unit 4 and the electrodes 31 a and31 b can be electrically connected only at the time of measurement.

(3) Measuring Unit 4

The measuring unit 4 is a part that measures the impedance of thebiological sample S obtained by an AC voltage being applied to thebiological sample S by the applying unit 3. Specifically, the impedanceof the biological sample S between the electrodes 31 a and 31 b ismeasured from, as the starting time point, the time point at which anorder to start measurement is received or the time point at which thepower supply for the impedance measuring device for biological samples 1is set to ON.

A dielectric constant etc. can be derived from the measured impedance.For the derivation of the dielectric constant, a known function ormathematical relation expressing the relationship between the impedanceand the dielectric constant may be used.

In the measuring unit 4, the frequency band in which the impedance ismeasured may be appropriately selected in accordance with the type,condition, measurement objective, etc. of the biological sample to bemeasured. For example, when the biological sample is blood, a change isseen in the impedance in the frequency bands shown in Table 1 below inaccordance with the condition change of the blood.

TABLE 1 Impedance Frequency at which Condition change of Frequency atwhich change is more blood change is seen significant Coagulation ofblood 1 kHz to 50 MHz 3 MHz to 15 MHz (blood coagulation) Fibrinformation 1 kHz to 50 MHz 3 MHz to 15 MHz Fibrin clot formation 1 kHz to50 MHz 3 MHz to 15 MHz Blood clot formation 1 kHz to 50 MHz 3 MHz to 15MHz Rouleaux formation of 500 kHz to 25 MHz 2 MHz to 10 MHz red bloodcells Aggregation of blood 1 kHz to 50 MHz 500 kHz to 5 MHzSedimentation of red 1 kHz to 50 MHz 100 kHz to 40 MHz blood cells(erythrocyte sedimentation) Blood clot retraction 1 kHz to 50 MHz 10 kHzto 100 kHz (retraction) Hemolysis 1 kHz to 50 MHz 3 MHz to 15 MHzFibrinolysis 1 kHz to 50 MHz 3 MHz to 15 MHz

For example, in the case where the objective is to predict or detect thecoagulation of blood (blood coagulation), it is preferable to measurethe impedance at frequencies of 1 kHz to 50 MHz, and it is morepreferable to measure the impedance at frequencies of 3 MHz to 15 MHz.By setting a parameter in accordance with the condition or measurementobjective of blood beforehand in this way, a preferable frequency bandlike those shown in Table 1 above can be automatically selected.

In the measuring unit 4, it is also possible to perform a plurality ofmeasurements. As the method for performing a plurality of measurements,for example, a method in which a plurality of measurements are performedsimultaneously by a plurality of measuring units 4 being provided, amethod in which a plurality of measurements are performed by scanningone measuring unit 4, a method in which a plurality of measurements areperformed by moving the biological sample holding unit 2, a method inwhich a plurality of measuring units 4 are provided and switching isperformed to select one or a plurality of measuring units 4 thatactually perform measurement, etc. may be given.

(4) Measurement Condition Control Unit 5

The measurement condition control unit 5 is a part that controls themeasuring time and/or the measuring frequency in the measuring unit 4.

For example, as a specific method for controlling the measuring time, itis possible to control the measuring interval in accordance with theamount of data necessary for the analysis of the objective or the like,or it is possible to control the timing of measurement completion whenthe measured value has almost leveled off or the like.

It is also possible to control the measuring frequency in accordancewith the type of the biological sample S of the measuring object, themeasured value necessary for the analysis of the objective, etc. As thecontrol of the measuring frequency, a method in which the frequency ofthe AC voltage applied between the electrodes 31 a and 31 b is changed,a method in which a plurality of frequencies are superposed to performimpedance measurement at the plurality of frequencies, etc. are given.As specific methods thereof, a method in which a plurality ofsingle-frequency analyzers are juxtaposed, a method in which thefrequency is swept, a method in which frequencies are superposed and theinformation of each frequency is extracted with a filter, a method inwhich measurement is performed using the response to an impulse, etc.are given.

(5) Temperature Control Unit 6

The temperature control unit 6 is a part that controls the temperaturein the biological sample holding unit 2. In the impedance measuringdevice for biological samples 1 according to the present technology,although the temperature control unit 6 is not an essential part, it ispreferably included in order to keep the biological sample S of themeasuring object in an optimum state for measurement.

As described later, in the case where the sample standby unit 12 isprovided, the temperature control unit 6 may control the temperature inthe sample standby unit 12. In the case where a drug is put in thebiological sample S at the time of or before measurement, thetemperature control unit 6 may be provided in order to control thetemperature of the drug. In this case, the temperature control unit 6may be provided individually for the temperature control in thebiological sample holding unit 2, the temperature control in the samplestandby unit 12, and the temperature control of the drug, or onetemperature control unit 6 may perform the temperature control of all ofthem.

Specific temperature control methods are not particularly limited. Forexample, the container holding unit 22 shown in FIG. 2 and FIG. 3 may beprovided with a temperature adjustment function; thereby, the containerholding unit 22 can be made to function as the temperature control unit6.

(6) Biological Sample Supplying Unit 7

The biological sample supplying unit 7 is a part that automaticallysupplies the biological sample S to the biological sample holding unit2. In the impedance measuring device for biological samples 1 accordingto the present technology, although the biological sample supplying unit7 is not an essential part, it is preferably included in order toperform each process automatically.

Specific methods for supplying the biological sample S are notparticularly limited. For example, when the biological sample S is in aliquid form, the biological sample S can be automatically supplied tothe biological sample holding unit 2 by using a pipetter and a chipattached to its tip. In this case, the chip is preferably used only onceand then thrown away in order to prevent measurement errors etc. It isalso possible to automatically supply the biological sample S to thebiological sample holding unit 2 from the storage chamber of thebiological sample S using a pump or the like. Furthermore, it is alsopossible to automatically supply the biological sample S to thebiological sample holding unit 2 using a permanent nozzle or the like.In this case, the nozzle is preferably provided with a cleaning functionin order to prevent measurement errors etc.

(7) Drug Supplying Unit 8

The drug supplying unit 8 is a part that automatically supplies one ormore kinds of drug to the biological sample holding unit 2. In theimpedance measuring device for biological samples 1 according to thepresent technology, although the drug supplying unit 8 is not anessential part, it is preferably included in order to perform eachprocess automatically.

Specific methods for supplying a drug are not particularly limited, anda drug may be supplied using similar methods to those for the biologicalsample supplying unit 7. In particular, the supply of a drug ispreferably performed by a method in which a certain amount of a drug canbe supplied without contacting the biological sample holding unit 2 (thecontainer 21). For example, a drug in a liquid form may be supplied bydischarge.

More specifically, for example, a liquid drug is introduced into adischarge pipe beforehand, and compressed air separately connected via apipe line connected to the discharge pipe is blown into the pipe linefor a short time; thereby, the liquid drug can be discharged andsupplied to the biological sample holding unit 2 (the container 21). Atthis time, the amount of the discharged liquid drug can be adjusted byadjusting the air pressure and the valve opening/closing time.

As well as blowing air, it is also possible to discharge and supply aliquid drug to the biological sample holding unit 2 (the container 21)by utilizing the vaporization of the liquid drug itself or air dissolvedtherein by heating. At this time, the amount of the discharged liquiddrug can be adjusted by adjusting the volume of generated air bubbles byadjusting the voltage applied to a vaporization chamber equipped with aheating element or the like and the time of voltage application.

Furthermore, a liquid drug may be supplied to the biological sampleholding unit 2 (the container 21) also by, not using air, driving amovable part provided in a pipe line using a piezoelectric element orthe like and sending the liquid drug in the amount determined by thecapacity of the movable part.

Furthermore, a drug may be supplied also by, for example, using what iscalled an inkjet system in which a liquid drug is made into minutedroplets and directly sprayed on the designated biological sampleholding unit 2 (the container 21).

The drug supplying unit 8 may be provided with a stirring function, atemperature control function, a discrimination function fordiscriminating the type of the drug or the like (e.g. a bar codereader), etc.

When using a drug, a prescribed drug may be stored in the container 21beforehand in a solidified form or a liquid form as it is. For example,when a biological sample S containing a blood component or the like isused as the measuring object, an anticoagulant, a coagulation initiator,etc. may be put in the container 21 beforehand.

Thus, by storing a drug in the container 21 beforehand, the drugsupplying unit 8 and a drug holding unit become unnecessary, anddownsizing of the device and reduction in costs are possible.Furthermore, the time and effort of drug exchange by a user etc. becomesunnecessary, and also the equipment maintenance of the drug supplyingunit 8 and the drug holding unit becomes unnecessary; thus, usabilitycan be improved.

(8) Biological Sample S

The biological sample S that can be the measuring object in the presenttechnology is not particularly limited, and may be freely selected. Inthe impedance measuring device for biological samples 1 according to thepresent technology, in particular the impedance of a biological samplein a liquid form or a gel form can be suitably measured. Specificexamples of the biological sample S in a liquid form include abiological sample S containing a blood component such as whole blood,blood plasma, or a diluted solution and/or a drug-added substancethereof, etc.

(9) Blood Condition Analyzing Unit 9

The blood condition analyzing unit 9 is a part that analyzes thecondition change of blood from the temporal change of the impedancemeasured in the measuring unit 4. In the impedance measuring device forbiological samples 1 according to the present technology, the bloodcondition analyzing unit 9 is not an essential part; but when abiological sample containing a blood component is used as the biologicalsample S, the condition change of blood can be detected by providing theblood condition analyzing unit 9.

More specifically, for example, the measured values of a plurality ofimpedances are received during the analysis period, a parameterexpressing the feature of each is extracted from the measured values,and the parameter and standard values determining the standards ofcondition changes of blood are compared; thus, the condition change ofblood can be analyzed on the basis of the comparison.

In the blood condition analyzing unit 9 in the present technology,specific examples of the condition change of blood analyzable are notparticularly limited to the extent that they are phenomena in which atemporal change in impedance is seen due to a condition change, andvarious condition changes can be detected and analyzed. For example, thecoagulation of blood (blood coagulation), fibrin formation, fibrin clotformation, blood clot formation, blood platelet coagulation, therouleaux formation of red blood cells, the aggregation of blood, thesedimentation of red blood cells (erythrocyte sedimentation), blood clotretraction, hemolysis such as fibrinolysis, fibrinolysis, etc. may begiven.

(10) Precision Managing Unit 10

The precision managing unit 10 is a part that performs the precisionmanagement of the measuring unit 4. In the impedance measuring devicefor biological samples 1 according to the present technology, althoughthe precision managing unit 10 is not an essential part, providing theprecision managing unit 10 makes it possible to improve the measurementprecision in the measuring unit 4.

Specific methods for managing the precision of the measuring unit 4performed in the precision managing unit 10 are not particularlylimited, and known precision managing methods may be freely selected foruse. For example, the method is not limited to methods in which theprecision management of the measuring unit 4 is performed by calibratingthe measuring unit 4, such as a method in which a metal plate or thelike for short-circuiting is installed in the device 1 and beforestarting measurement the electrodes and the metal plate areshort-circuited to calibrate the measuring unit 4, a method in which ajig for calibration or the like and the electrodes are brought intocontact, and a method in which a container with an identicalconfiguration to the container 21 for storing a biological sample isequipped with a metal plate or the like and before starting measurementthe electrodes and the metal plate are short-circuited to calibrate themeasuring unit 4; and precision management may be performed also byusing an arbitrary method such as a method in which the precisionmanagement of the measuring unit 4 is performed by checking thecondition of the measuring unit 4 before actual measurement, and onlyupon the occurrence of abnormality, calibrating the measuring unit 4 byperforming calibration like the above etc.

(11) Driving Mechanism 11

The driving mechanism 11 is used to move the biological sample holdingunit 2 in accordance with various purposes. For example, when abiological sample S containing sedimentous components is used as themeasuring object, the biological sample holding unit 2 may be moved in adirection that changes the direction of the gravity applied to thebiological sample S held by the biological sample holding unit 2; thus,the measured value can be prevented from being influenced bysedimentation of the sedimentous components.

Furthermore, for example like the biological sample holding unit 2 shownin FIG. 3 above, the applying unit 3 and the electrodes 31 a and 31 bare set to a non-connection state at the time of non-measurement, and atthe time of measurement the biological sample holding unit 2 may bedriven so that the applying unit 3 and the electrodes 31 a and 31 b canbe electrically connected.

Furthermore, for example, in the case where a plurality of biologicalsample holding units 2 are provided, when the biological sample holdingunit 2 is configured to be movable like the example shown in FIG. 4,measurement, biological sample supply, drug supply, etc. can beperformed by moving the biological sample holding unit 2 to a neededpart. That is, since there is no need to move the measuring unit 4, thebiological sample supplying unit 7, the drug supplying unit 8, etc. tothe biological sample holding unit 2 of the objective, there is no needto provide a driving unit for driving these units etc. and downsizing ofthe device and reduction in costs are possible.

(12) Sample Standby Unit 12

The sample standby unit 12 is a part that allows aliquoted biologicalsamples S to stand by before measurement. In the impedance measuringdevice for biological samples 1 according to the present technology,although the sample standby unit 12 is not an essential part, it may beincluded in order to perform measurement smoothly.

The sample standby unit 12 may be provided with a stirring function, atemperature control function, a mechanism of movement to the biologicalsample holding unit 2, a discrimination function for discriminating thetype of the biological sample S etc. (e.g. a bar code reader etc.), anautomatic opening function, etc.

(13) Stirring Mechanism 13

The stirring mechanism 13 is a mechanism that performs stirring in thebiological sample holding unit 2. More specifically, the stirringmechanism 13 is a mechanism for stirring the biological sample S itselfheld in the biological sample holding unit 2 and stirring the biologicalsample S and a drug such as a reagent. In the impedance measuring devicefor biological samples 1 according to the present technology, althoughthe stirring mechanism 13 is not an essential part, it is preferablyincluded, for example when sedimentous components are contained in thebiological sample S, when a drug such as a reagent is added at the timeof measurement, or in other cases. More specifically, for example, whenblood is used as the biological sample S, the sedimentation of red bloodcells (erythrocyte sedimentation) can be prevented by stirring bloodwith the stirring mechanism 13.

Specific stirring methods in the stirring mechanism 13 are notparticularly limited to the extent that the effect of the presentinvention is not impaired, and known stirring methods may be freelyselected for use. For example, stirring by pipetting, stirring using astirring rod, a stirring chip, or the like, stirring by inverting acontainer containing the biological sample S and a drug, etc. may begiven.

A specific example of the stirring method will now be described withreference to the drawing. FIG. 5 is a conceptual diagram showing astirring method in the case where the biological sample S and a reagentR are stirred by pipetting using the stirring mechanism 13.

<Step 1>

In step 1, the biological sample S of the measurement objective isinjected beforehand into the biological sample holding unit 2 in which areagent R is held. To introduce the reagent R into the biological sampleholding unit 2, the reagent R may be automatically injected into thebiological sample holding unit 2 beforehand using the drug supplyingunit 8 described above, or a cartridge in which the reagent R is heldbeforehand may be used as the biological sample holding unit 2.

The injection of the biological sample S into the biological sampleholding unit 2 may be automatically performed by, for example, thebiological sample supplying unit 7 described above. Although thebiological sample S is discharged in a bottom portion of the biologicalsample holding unit 2 in the example shown in FIG. 5, the dischargeposition is not limited to this, and it is also possible to set aparameter in accordance with the type, condition, etc. of the biologicalsample S beforehand and automatically control the discharge position.

<Step 2>

In step 2, the biological sample S and/or the reagent R is sucked from aprescribed position of the biological sample holding unit 2. Althoughthe suction is performed in a bottom portion of the biological sampleholding unit 2 in the example shown in FIG. 5, the suction position isnot limited to this, and it is also possible to set a parameter inaccordance with the type, condition, etc. of the biological sample Sbeforehand and automatically control the suction position.

As the pipette used in the pipetting of step 2 and step 3 describedlater, the pipette used for the injection of the biological sample S instep 1 may be used as it is, or another pipette may be used.

<Step 3>

In step 3, the biological sample S and/or the reagent R sucked in step 2is discharged from a prescribed position of the biological sampleholding unit 2. Although the discharge is performed in a central portionof the biological sample holding unit 2 in the example shown in FIG. 5,the discharge position is not limited to this, and it is also possibleto set a parameter in accordance with the type, condition, etc. of thebiological sample S beforehand and automatically control the dischargeposition.

Step 2 and step 3 are taken as one set and pipetting is repeatednecessary times; thereby, the biological sample S and the reagent R canbe stirred. Although the biological sample S and the reagent R arestirred by repeating step 2 and step 3 for three sets in the exampleshown in FIG. 5, the number of times of pipetting is not limited tothis, and it is also possible to set a parameter in accordance with thetypes, conditions, amounts, etc. of the biological sample S and thereagent R beforehand and automatically control the number of times ofstirring allowable.

2. Impedance Measuring System for Biological Samples 100

FIG. 6 is a schematic conceptual diagram schematically showing theconcept of an impedance measuring system for biological samples 100according to the present technology. The impedance measuring system forbiological samples 100 according to the present technology includes, interms of broad categories, at least the biological sample holding unit2, the applying unit 3, the measuring unit 4, the measurement conditioncontrol unit 5, a display unit 101, and a user interface 102. Theimpedance measuring system for biological samples 100 may include, asnecessary, the temperature control unit 6, the biological samplesupplying unit 7, the drug supplying unit 8, the blood conditionanalyzing unit 9, the precision managing unit 10, the driving mechanism11, a memory unit 103, etc. Each component will now be described indetail. The biological sample holding unit 2, the applying unit 3, themeasuring unit 4, the measurement condition control unit 5, thetemperature control unit 6, the biological sample supplying unit 7, thedrug supplying unit 8, the blood condition analyzing unit 9, theprecision managing unit 10, and the driving mechanism 11 are the same asthose of the impedance measuring device for biological samples 1described above, and a description is omitted herein.

(1) Display Unit 101

The display unit 101 is a part that displays the data of the impedancemeasured in the measuring unit 4. The display unit 101 may display thenumerical data of the impedance measured in the measuring unit 4 as theyare, or may display a graph of the data, for example. FIG. 7 shows anexample of data displayed on the display unit 101.

It is also possible to use the data of the impedance measured in themeasuring unit 4 to analyze the properties etc. of the biological sampleS and display the analyzed data.

(2) User Interface 102

The user interface 102 is a part for a user's operation. A user canaccess each part of the impedance measuring device for biologicalsamples 1 according to the present technology through the user interface102.

(3) Memory Unit 103

The memory unit 103 is a part that stores the data of the impedancemeasured in the measuring unit 4. The memory unit 103 may store the dataof the impedance measured in the measuring unit 4 as they are, or maystore analyzed data obtained by analyzing the properties etc. of thebiological sample S using the data of the impedance measured in themeasuring unit 4.

In the impedance measuring system for biological samples 100 accordingto the present technology described above, the impedance measuringdevice for biological samples 1, the display unit 101, the userinterface 102, and the memory unit 103 may be connected to each othervia a network.

Additionally, the present technology may also be configured as below.

-   (1)

An impedance measuring device for biological samples including:

one or a plurality of biological sample holding units configured to holda biological sample;

an applying unit configured to apply an AC voltage to a pair ofelectrodes in contact with the biological sample held by the biologicalsample holding unit;

a measuring unit configured to measure an impedance of the biologicalsample obtained by an AC voltage being applied to the biological sampleby the applying unit; and

a measurement condition control unit configured to control a measuringtime and/or a measuring frequency in the measuring unit.

-   (2)

The impedance measuring device for biological samples according to (1),wherein in control of the measuring time in the measurement conditioncontrol unit, a measuring interval in the measuring unit is controlled.

-   (3)

The impedance measuring device for biological samples according to (1)or (2), wherein in control of the measuring time in the measurementcondition control unit, a timing of measurement completion in themeasuring unit is controlled.

-   (4)

The impedance measuring device for biological samples according to anyone of (1) to (3), further including:

a temperature control unit configured to control a temperature in thebiological sample holding unit.

-   (5)

The impedance measuring device for biological samples according to anyone of (1) to (4), wherein in the biological sample holding unit, abiological sample is held by holding a container in which the biologicalsample is stored.

-   (6)

The impedance measuring device for biological samples according to (5),further including:

a biological sample supplying unit configured to supply the biologicalsample to the biological sample holding unit automatically.

-   (7)

The impedance measuring device for biological samples according to (5)or (6), further including:

a drug supplying unit configured to supply one or more kinds of drug tothe biological sample holding unit automatically.

-   (8)

The impedance measuring device for biological samples according to (5)or (6), wherein one or more kinds of drug are stored in the containerbeforehand.

-   (9)

The impedance measuring device for biological samples according to anyone of (1) to (8), wherein the biological sample contains a bloodcomponent.

-   (10)

The impedance measuring device for biological samples according to (9),further including:

a blood condition analyzing unit configured to analyze a conditionchange of blood from a temporal change of an impedance measured in themeasuring unit.

-   (11)

The impedance measuring device for biological samples according to anyone of (1) to (10), further including:

a precision managing unit configured to perform management of precisionof the measuring unit.

-   (12)

The impedance measuring device for biological samples according to anyone of (1) to (11), further including:

a driving mechanism configured to move the biological sample holdingunit.

-   (13)

The impedance measuring device for biological samples according to (12),wherein the driving mechanism moves the biological sample holding unitin a direction that changes a direction of gravity applied to thebiological sample held by the biological sample holding unit.

-   (14)

The impedance measuring device for biological samples according to anyone of (1) to (12), further including:

a stirring mechanism configured to perform stirring in the biologicalsample holding unit.

-   (15)

An impedance measuring system for biological samples including:

one or a plurality of biological sample holding units configured to holda biological sample;

an applying unit configured to apply an AC voltage to a pair ofelectrodes in contact with the biological sample held by the biologicalsample holding unit;

a measuring unit configured to measure an impedance of the biologicalsample obtained by an AC voltage being applied to the biological sampleby the applying unit;

a measurement condition control unit configured to control a measuringtime and/or a measuring frequency in the measuring unit;

a display unit configured to display data of an impedance measured inthe measuring unit; and

a user interface for a user's operation.

-   (16)

The impedance measuring system for biological samples according to (15),further including:

a memory unit configured to store data of an impedance measured in themeasuring unit.

INDUSTRIAL APPLICABILITY

The impedance measuring device and system for biological samplesaccording to the present technology can automatically control themeasuring time and/or the measuring frequency, and can therefore, in theimpedance measurement of a biological sample, improve measurementprecision rapidly in accordance with the type, analysis objective, etc.of the biological sample.

REFERENCE SIGNS LIST

-   1 impedance measuring device for biological samples-   2 biological sample holding unit-   21 container-   22 container holding unit-   3 applying unit-   31 a, 31 b electrode-   32 connection unit-   4 measuring unit-   5 measurement condition control unit-   6 temperature control unit-   7 biological sample supplying unit-   8 drug supplying unit-   9 blood condition analyzing unit-   10 precision managing unit-   11 driving mechanism-   12 sample standby unit-   13 stirring mechanism-   100 impedance measuring system for biological samples-   101 display unit-   102 user interface-   103 memory unit-   R reagent-   S biological sample

The invention claimed is:
 1. A method of operating an impedancemeasuring device for biological samples comprising: applying an ACvoltage to a pair of electrodes connected to a biological sample holdingunit; measuring an impedance of a biological sample by applying an ACvoltage to the pair of electrodes; controlling a measuring time and/or ameasuring frequency when applying the AC voltage; and calibrating theimpedance measuring device based on an electrical connection between thepair of electrodes.
 2. The method according to claim 1, wherein incontrol of the measuring time, a measuring interval is controlled. 3.The method according to claim 1, wherein in control of the measuringtime, a timing of measurement completion is controlled.
 4. The methodaccording to claim 1, further comprising controlling a temperature inthe biological sample holding unit.
 5. The method according to claim 1,wherein in the biological sample holding unit, the biological sample isheld by holding a container in which the biological sample is stored. 6.The method according to claim 1, further comprising supplying, by abiological sample supplying unit, the biological sample to thebiological sample holding unit automatically.
 7. The method according toclaim 1, further comprising supplying, by a drug supplying unit, one ormore kinds of drugs to the biological sample holding unit automatically.8. The method according to claim 5, wherein one or more kinds of drugare stored in the container beforehand.
 9. The method according to claim1, wherein the biological sample contains a blood component.
 10. Themethod according to claim 9, further comprising analyzing a conditionchange of blood from a temporal change of the measured impedance. 11.The method according to claim 1, wherein the calibrating of theimpedance measuring device is executed in response to detecting anabnormality of the impedance measuring device.
 12. The method accordingto claim 1, further comprising moving, by a driving mechanism, thebiological sample holding unit.
 13. The method according to claim 12,wherein the driving mechanism moves the biological sample holding unitin a direction that changes a direction of gravity applied to thebiological sample held by the biological sample holding unit.
 14. Themethod according to claim 1, further comprising stirring the biologicalsample by a stirring mechanism that is configured to perform stirring inthe biological sample holding unit.
 15. A method of measuring impedancefor biological samples with an impedance measuring system, the methodcomprising: holding one or a plurality of biological samples in one or aplurality of biological sample holding units; applying an AC voltage toa pair of electrodes in contact with a first biological sample held by afirst biological sample holding unit of the one or a plurality ofbiological sample holding units; measuring an impedance of the firstbiological sample based on the AC voltage applied to the pair ofelectrodes; controlling a measuring time and/or a measuring frequencywhen applying the AC voltage; calibrating the impedance measuring systembased on an electrical connection between the pair of electrodes;displaying impedance data that is representative of an impedancemeasured based on the applied AC voltage; and displaying a userinterface for a user's operation.
 16. The method according to claim 15,further comprising storing, in a memory unit, at least some of theimpedance data.